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Biomedical subjects

V Kipnis

Publications and source records attributed to V Kipnis.

At least 19 recordsLinked to original sources

Precision of the doubly labeled water method in a large-scale application: evaluation of a streamlined-dosing protocol in the Observing Protein and Energy Nutrition (OPEN) study.

OBJECTIVE: To evaluate whether the doubly labeled water (DLW) method is precise under conditions required for a large-scale evaluation of dietary intake instruments. DESIGN: Energy expenditure was measured in 484 subjects (main study). Subjects received one of five different weight DLW dose bottles prepared in advance of the study. A repeat energy expenditure measure was obtained in a subset of 24 subjects (substudy). DLW measures of energy expenditure were performed over a 2-week interval with urine collection at the beginning and end. SETTING: Free-living environment with three clinic visits in the Maryland suburban area of Washington, DC. SUBJECTS: A total of 484 subjects (261 men and 223 women) aged 40-69 y, 24 of whom (13 men and 11 women) participated in a substudy in which DLW was administered a second time. RESULTS: The coefficient of variation of the DLW energy expenditure measurement was 5.1%. This included a 2.9% analytical and a 4.2% physiologic variation. Based on observed initial isotopic enrichment, the preweighed dosages were optimal in 70% of the main study subjects, and 9% received a dose that was less than optimal. Only six subjects (1%) were excluded because the final isotopic enrichment was too low to conduct precise measurement. CONCLUSIONS: Use of preweighed DLW dosages did not compromise the precision of the DLW method. The DLW method is a reliable measure of energy expenditure for large-scale evaluations of dietary intake instruments.

Adult↗

Comparative validation of the Block, Willett, and National Cancer Institute food frequency questionnaires : the Eating at America's Table Study.

Researchers at the National Cancer Institute developed a new cognitively based food frequency questionnaire (FFQ), the Diet History Questionnaire (DHQ). The Eating at America's Table Study sought to validate and compare the DHQ with the Block and Willett FFQs. Of 1,640 men and women recruited to participate from a nationally representative sample in 1997, 1,301 completed four telephone 24-hour recalls, one in each season. Participants were randomized to receive either a DHQ and Block FFQ or a DHQ and Willett FFQ. With a standard measurement error model, correlations for energy between estimated truth and the DHQ, Block FFQ, and Willett FFQ, respectively, were 0.48, 0.45, and 0.18 for women and 0.49, 0.45, and 0.21 for men. For 26 nutrients, correlations and attenuation coefficients were somewhat higher for the DHQ versus the Block FFQ, and both were better than the Willett FFQ in models unadjusted for energy. Energy adjustment increased correlations and attenuation coefficients for the Willett FFQ dramatically and for the DHQ and Block FFQ instruments modestly. The DHQ performed best overall. These data show that the DHQ and the Block FFQ are better at estimating absolute intakes than is the Willett FFQ but that, after energy adjustment, all three are more comparable for purposes of assessing diet-disease risk.

Adult↗

Design and serendipity in establishing a large cohort with wide dietary intake distributions : the National Institutes of Health-American Association of Retired Persons Diet and Health Study.

In 1995-1996, the authors mailed a food frequency questionnaire to 3.5 million American Association of Retired Persons members who were aged 50-69 years and who resided in one of six states or two metropolitan areas with high-quality cancer registries. In establishing a cohort of 567,169 persons (340,148 men and 227,021 women), the authors were fortunate in that a less-than-anticipated baseline response rate (threatening inadequate numbers of respondents in the intake extremes) was offset by both a shifting and a widening of the intake distributions among those who provided satisfactory data. Reported median intakes for the first and fifth intake quintiles, respectively, were 20.4 and 40.1 (men) and 20.1 and 40.0 (women) percent calories from fat, 10.3 and 32.0 (men) and 8.7 and 28.7 (women) g per day of dietary fiber, 3.1 and 11.6 (men) and 2.8 and 11.3 (women) servings per day of fruits and vegetables, and 20.7 and 156.8 (men) and 10.5 and 97.0 (women) g per day of red meat. After 5 years of follow-up, the cohort is expected to yield nearly 4,000 breast cancers, more than 10,000 prostate cancers, more than 4,000 colorectal cancers, and more than 900 pancreatic cancers. The large size and wide intake range of the cohort will provide ample power for examining a number of important diet and cancer hypotheses.

Aged↗

Empirical evidence of correlated biases in dietary assessment instruments and its implications.

Multiple-day food records or 24-hour recalls are currently used as "reference" instruments to calibrate food frequency questionnaires (FFQs) and to adjust findings from nutritional epidemiologic studies for measurement error. The common adjustment is based on the critical requirements that errors in the reference instrument be independent of those in the FFQ and of true intake. When data on urinary nitrogen level, a valid reference biomarker for nitrogen intake, are used, evidence suggests that a dietary report reference instrument does not meet these requirements. In this paper, the authors introduce a new model that includes, for both the FFQ and the dietary report reference instrument, group-specific biases related to true intake and correlated person-specific biases. Data were obtained from a dietary assessment validation study carried out among 160 women at the Dunn Clinical Nutrition Center, Cambridge, United Kingdom, in 1988-1990. Using the biomarker measurements and dietary report measurements from this study, the authors compare the new model with alternative measurement error models proposed in the literature and demonstrate that it provides the best fit to the data. The new model suggests that, for these data, measurement error in the FFQ could lead to a 51% greater attenuation of true nutrient effect and the need for a 2.3 times larger study than would be estimated by the standard approach. The implications of the results for the ability of FFQ-based epidemiologic studies to detect important diet-disease associations are discussed.

Bias↗

Efficient regression calibration for logistic regression in main study/internal validation study designs with an imperfect reference instrument.

An extension to the version of the regression calibration estimator proposed by Rosner et al. for logistic and other generalized linear regression models is given for main study/internal validation study designs. This estimator combines the information about the parameter of interest contained in the internal validation study with Rosner et al.'s regression calibration estimate, using a generalized inverse-variance weighted average. It is shown that the validation study selection model can be ignored as long as this model is jointly independent of the outcome and the incompletely observed covariates, conditional, at most, upon the surrogates and other completely observed covariates. In an extensive simulation study designed to follow a complex, multivariate setting in nutritional epidemiology, it is shown that with validation study sizes of 340 or more, this estimator appears to be asymptotically optimal in the sense that it is nearly unbiased and nearly as efficient as a properly specified maximum likelihood estimator. A modification to the regression calibration variance estimator which replaces the standard uncorrected logistic regression coefficient variance with the sandwich estimator to account for the possible misspecification of the logistic regression fit to the surrogate covariates in the main study, was also studied in this same simulation experiment. In this study, the alternative variance formula yielded results virtually identical to the original formula. A version of the proposed estimator is also derived for the case where the reference instrument, available only in the validation study, is imperfect but unbiased at the individual level and contains error that is uncorrelated with other covariates and with error in the surrogate instrument. Replicate measures are obtained in a subset of study participants. In this case it is shown that the validation study selection model can be ignored when sampling into the validation study depends, at most, only upon perfectly measured covariates. Two data sets, a study of fever in relation to occupational exposure to antineoplastics among hospital pharmacists and a study of breast cancer incidence in relation to dietary intakes of alcohol and vitamin A, adjusted for total energy intake, from the Nurses' Health Study, were analysed using these new methods. In these data, because the validation studies contained less than 200 observations and the events of interest were relatively rare, as is typical, the potential improvements offered by this new estimator were not apparent.

Adult↗

Evaluation of alternative approaches to assign nutrient values to food groups in food frequency questionnaires.

Although every food frequency questionnaire (FFQ) requires a nutrient database to produce nutrient intake estimates, it is often unclear how a particular database has been generated. Moreover, alternative methods for constructing a database have not been rigorously evaluated. Using 24-hour recalls from the 1994-1996 Continuing Survey of Food Intake by Individuals, the authors categorized 5,261 individual foods reported by 10,019 adults into 170 food groups consistent with line items on an FFQ. These food groups were used to generate 10 potential nutrient databases for a FFQ that varied by whether the authors 1) used means or medians, 2) did or did not consider age, 3) incorporated collapsing strategies for small age-gender-portion size cells, 4) excluded outliers in a regression, and 5) used weighted median nutrient density x age-gender-portion size-specific median gram weights (Block method). Mean error, mean squared error, and mean absolute error were calculated and compared across methods, with error being the difference in total observed (from recalls for each individual) and total estimated intake (from each of the 10 methods) for seven nutrients. Mean methods for assigning nutrients to food groups were superior to median approaches for all measurements. Among the mean methods, no single variation was consistently better.

Adult↗

Evaluation of 2 brief instruments and a food-frequency questionnaire to estimate daily number of servings of fruit and vegetables.

BACKGROUND: Measurement of fruit and vegetable intake is important in the surveillance of populations and in epidemiologic studies that examine the relations between diet and disease. Some situations require the use of brief dietary assessment tools. OBJECTIVE: Our objective was to evaluate the performance of 2 brief dietary assessment instruments, a 7-item standard screener and a new 16-item screener, and a complete food-frequency questionnaire (FFQ) in measuring total fruit and vegetable consumption. DESIGN: About 800 men and women from the National Institutes of Health-AARP Diet and Health Study completed an FFQ, 1 of the 2 screeners, and two 24-h dietary recalls. Fruit and vegetable intakes as measured by each screener and the FFQ were compared with estimated true usual intake by using a measurement-error model. RESULTS: Median daily servings of fruit and vegetables were underestimated by both screeners. The estimated agreement between true intake and the screener was higher for the new screener than for the standard screener and was higher for women than for men. The estimated agreement between true intake and the FFQ was higher than that for both screeners. Attenuation coefficients for the FFQ and screeners were comparable. CONCLUSIONS: For estimating median intakes of fruit and vegetables and the prevalence of recommended intakes being met, the use of screeners without appropriate adjustment is suboptimal. For estimating relative risks in the relations between fruit and vegetable intake and disease, screeners and this FFQ are similar in performance.

Aged↗

Implications of a new dietary measurement error model for estimation of relative risk: application to four calibration studies.

Food records or 24-hour recalls are currently used to calibrate food frequency questionnaires (FFQs) and to correct disease risks for measurement error. The standard regression calibration approach requires that these reference measures contain only random within-person errors uncorrelated with errors in FFQs. Increasing evidence suggests that records/recalls are likely to be also flawed with systematic person-specific biases, so that for any individual the average of multiple replicate assessments may not converge to her/his true usual nutrient intake. The authors propose a new measurement error model to accommodate person-specific bias in the reference measure and its correlation with systematic error in the FFQ. Sensitivity analysis using calibration data from four studies demonstrates that failure to account for person-specific bias in the reference measure can often lead to substantial underestimation of the relative risk for a nutrient. These results indicate that in the absence of information on the extent of person-specific biases in reference instruments and their relation to biases in FFQs, the adequacy of the standard methods of correcting relative risks for measurement error is in question, as is the interpretation of negative findings from nutritional epidemiology such as failure to detect an important relation between fat intake and breast cancer.

Bias↗

Measurement error and dietary intake.

This chapter reviews work of Carroll, Freedman, Kipnis, and Li (1998) on the statistical analysis of the relationship between dietary intake and health outcomes. In the area of nutritional epidemiology, there is some evidence from biomarker studies that the usual statistical model for dietary measurements may break down due to two causes: (a) systematic biases depending on a person's body mass index; and (b) an additional random component of bias, so that the error structure is the same as a one-way random effects model. We investigate this problem, in the context of (1) the estimation of the distribution of usual nutrient intake; (2) estimating the correlation between a nutrient instrument and usual nutrient intake; and (3) estimating the true relative risk from an estimated relative risk using the error-prone covariate. While systematic bias due to body mass index appears to have little effect, the additional random effect in the variance structure is shown to have a potentially important impact on overall results, both on corrections for relative risk estimates and in estimating the distribution usual of nutrient intake. Our results point to a need for new experiments aimed at estimation of a crucial parameter.

Bias↗

Effect of measurement error on energy-adjustment models in nutritional epidemiology.

The use and interpretation of energy-adjustment regression models in nutritional epidemiology has been vigorously debated recently. There has been little discussion, however, regarding the effect of dietary measurement error on the performance of such models. Contrary to conventional assumptions invoked in the standard treatment of the effect of measurement error in regression analysis, reporting errors in dietary studies are usually biased, correlated with true nutrient intakes and with each other, heteroscedastic, and nonnormally distributed. Methods developed in this paper allow for this more complex error structure and are therefore more appropriate for dietary data. For practical illustration, these methods are applied to data from the Women's Health Trial Vanguard Study. The results demonstrate considerable shrinkage in the magnitude of the estimated main exposure effect in energy-adjustment models due to attenuation of the true effect and contamination from the effect of an adjusting covariate. In most cases, this shrinkage causes a sharply reduced statistical power of the corresponding significance test in comparison with measurement without error. These results emphasize the need to understand the measurement error properties of dietary instruments through validation/calibration studies and, where possible, to correct for the impact of measurement error when applying energy-adjustment models.

Aged↗

Relationship between static chemical and cyclic mechanical fatigue in a feldspathic porcelain.

OBJECTIVES: The goal of this study was to determine if static chemical and cyclic mechanical fatigue are independent, or if they interact to produce greater than additive strength loss in a feldspathic porcelain. METHODS: A blunt indentation technique was used to investigate the response of a feldspathic dental porcelain to cyclic mechanical fatigue and static chemical fatigue. All specimens were fabricated in a dry inert environment and then mechanically fatigued by cyclic loading and strength-tested in dry inert nitrogenous, ambient or wet environments. A series of experiments were performed to evaluate the effects of chemical and mechanical fatigue, and their interaction on strength loss; to determine the effects of, and interaction between, the factors of cyclic fatigue environment and strength test environment on strength; to ascertain if the type of environment during strength testing influenced specimen strength; and to distinguish between chemical damage caused by exposure to moisture alone and stress corrosion damage resulting from the strength testing environment, using a pair of two-way analysis of variance, a single one-way analysis of variance and a t-test (p < 0.05). RESULTS: These experiments indicated that both static chemical fatigue and cyclic mechanical fatigue significantly reduced specimen strength, but they did not interact to produce greater than summative effects. It was also learned that chemical fatigue was not detected on initial exposure to moisture and that it occurred to a small extent during mechanical fatigue cycling, and primarily occurred during strength testing through a stress-corrosion phenomenon. Micrographs visually evaluated the effects of mechanical and chemical fatigue on surface contact damage. SIGNIFICANCE: As both static chemical and cyclic mechanical fatigue influenced porcelain strength, they should both be considered in future evaluations. However, because they largely acted independently, they can be studied separately.

Aluminum Silicates↗

Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1.

A Siberian kindred with spinocerebellar ataxia genetically linked to the SCA1 locus on chromosome 6p has been screened for the CAG triplet expansion within the coding region of the SCA1 gene. The kindred includes 1,484 individuals, 225 affected and 656 at risk, making this collection the largest spinocerebellar ataxia type 1 (SCA1) pedigree known. Each of the studied 78 SCA1 patients carried an expanded allele containing a stretch of 39 to 72 uninterrupted CAG repeats. Normal alleles had 25 to 37 trinucleotide repeats. Expanded alleles containing 40 to 55 repeats were found in 26 at-risk relatives. The number of CAG repeats in the mutated allele was inversely correlated with age at disease onset. Cerebellar deficiency was present in each patient and its severity was moderately affected by the number of CAG repeats. In contrast, the associated signs, dysphagia, diffuse skeletal muscle atrophy with fasciculations, and tongue atrophy were absent or mild in patients with low CAG repeat numbers, but severely complicated the course of illness in patients with a larger number of repeat units. One female mutation carrier was asymptomatic at age 66, more than 2 standard deviations beyond the average age of risk, suggesting incomplete penetrance. In 2 symptomatic individuals who had an expanded number of CAG repeats on both chromosomes, age at onset, rate of progression, and clinical manifestation corresponded to the size of the larger allele.

Adolescent↗

Approached to monitoring the results of long-term disease prevention trials: examples from the Women's Health Initiative.

We contrast monitoring therapeutic trials with monitoring prevention trails. We argue that in monitoring prevention trials one should place more emphasis on formally defined global measures of health, not simply on a single targeted disease, particularly when an intervention may reduce the incidence of some diseases but increase the incidence of others. We describe one approach, illustrated by the Women's Health Initiative. For each of several sets of hypothetical interim results ("scenarios"), members of the Data and Safety Monitoring Committee (DSMC) were asked whether they would continue or stop the trial. In parallel with this exercise, various statistical methods of monitoring that are based on (1) the primary targeted disease, (2) a combination of various disease outcomes, or (3) a mixture of both were applied to these scenarios. One objective was to find a statistical approach that mirrors the majority view of the DSMC. A second objective was to stimulate discussion among DSMC members in preparation for their task of monitoring the trial as the real data become available. We found that no single method fully matched the majority vote of the DSMC. However, a mixed approach requiring the primary outcome to be significant and the global index to be "supportive," with separate monitoring of adverse effects, corresponded with the majority vote quite well. This approach maintains the emphasis on the primary hypothesis while assuring that broader safety and ethical issues of multiple diseases are incorporated.

Bayes Theorem↗

Effect of dynamic loading methods on cement film thickness in vitro.

PURPOSE: Reduced cement flm thicknesses can improve crown seating and decrease marginal discrepancies. Improved marginal adaptation has the potential to reduce plaque accumulation, periodontal disease, and cement dissolution. Studies have indicated that dynamic seating methods can reduce seating discrepancies associated with zinc phosphate and resin cements. However, other types of cements and other dynamic techniques have not yet been studied or compared, nor has the mechanism for improved seating been fully explained. Therefore, the purpose of this study was to investigate the effect of a variety of loading methods on the film thicknesses of current types of crown and fixed partial denture cements compressed between glass plates. MATERIALS AND METHODS: This study investigated the effect of three dynamic loading methods on film thickness of six representative fixed prosthodontic cements. These included zinc phosphate, resin-modified glass ionomer, encapsulated glass ionomer, adhesive composite resin, composite resin, and polycarboxylate. The method was derived from American Dental Association specifications for cement film thickness. In control groups, the cements were placed between two glass glass plates and statically loaded with a 15-kg weight. The test groups were initially similarly loaded, and then for 30 seconds further subjected to simulated repeated patient opening and closing, vibrations from an electromallet, or an ultrasonic device. RESULTS: Mean film thicknesses ranged from 7.4 micrometers for polycarboxylate / ultrasound up to 40.3 micrometers for composite resin / static. Two-way analysis of variance revealed that the effects of material type and cementation method and their interaction all significantly affected film thickness (P < .0001). Multiple range analysis showed that dynamic methods were generally superior to static loading and that the ultrasonic method was the best overall. CONCLUSIONS: The different dynamic loading methods all significantly decreased cement film thicknesses between glass plates. The ultrasonic method was the most effective. The type of cement used also influenced film thickness. Composite resins were more affected than other materials.

Analysis of Variance↗

Can energy adjustment separate the effects of energy from those of specific macronutrients?

Energy adjustment is used in nutritional epidemiology in an attempt to separate specific effects of macronutrients (carbohydrate, fat, and protein) from one another and from the generic effect of the total quantity of energy consumed. However, models in which the risk of disease is allowed to depend simultaneously on daily total energy consumption and separate components of energy that sum to the total are not identifiable: the specific effects of individual macronutrients and the generic effect of energy cannot be disentangled by multivariate analysis. The standard, residual, and partition methods exclude one or more macronutrients from consideration, thereby allowing estimation, but the parameters that are estimated no longer represent specific macronutrient or generic energy effects. Therefore, an interpretation of a regression coefficient from these methods as a specific effect of a macronutrient or as the generic effect of energy requires additional, almost always questionable, assumptions. For example, a conclusion based on data alone that there is a specific fat effect upon the development of breast cancer but no specific effects of other macronutrients and no generic energy effect is not possible. Notwithstanding these serious problems, some useful etiologic inference still can be made.

Energy Metabolism↗

Energy adjustment methods for nutritional epidemiology: the effect of categorization.

The authors discuss the interpretation of four alternative energy adjustment methods (Residual, Standard, Partition, and Nutrient Density) that have been proposed for the analysis of nutritional epidemiology studies. These methods have so far been compared under circumstances where intake of the nutrient of interest is measured as a continuous variable. Because it is common practice to categorize nutrient intakes in the analysis, the authors investigate the effect of such categorization on the interpretation of results from the four methods with the use of computer simulations and statistical theory. They consider four cases: where the nutrient intake is either divided into quartiles or ordered so as to investigate trend over the quartile groups, combined with using an adjusting variable that is either continuous or categorized. The results show: 1) the Residual, Standard, and Partition methods are no longer equivalent as they are in the continuous case; 2) compared with the Standard method, the Residual method appears to be more powerful for detecting trends in relative odds, is more robust to residual confounding when the adjustment variable is categorized, and provides more meaningful odds ratios; and 3) the Residual and Nutrient Density methods give closely similar results.

Bias↗

Influence of marginal opening on microleakage of cemented artificial crowns.

This study investigated the relationship between marginal opening and microleakage. Standardized preparations were made on intact human premolars, and copings were cast in a base metal alloy by use of conventional techniques. The castings were randomly assigned to the following luting agent groups: zinc phosphate cement, polycarboxylate cement, glass ionomer cement, phosphate ester composite resin, and a composite resin with a NPG-GMA dentinal bonding agent and were cemented in a standardized manner. The marginal openings between teeth and castings were measured, and microleakage was determined at the same points. Within the confines of the in vitro model used, no significant correlation between marginal opening and microleakage was established for either pooled data or individual luting agent groups.

Analysis of Variance↗